Pneumocystis carinii is a major pathogen of patients with HIV infection. The immune responses to P. carinii are poorly understood, but cytokines may play a role in both clearing P. carinii infection and in the hypoxia associated with P. carinii pneumonia that may be exacerbated following initiation of therapy. We are using the scid mouse model, as well as other immunodeficient mice, to further evaluate the role of individual cytokines and other immunoregulatory molecules in modulating P. carinii infection. We are in the process of developing techniques that will allow assessment of which cytokines are produced in response to P. carinii antigens. We have also developed a real time PCR assay for quantitative PCP over a wide dynamic range, and will be examining PCP infection in healthy animals to better understand immune responses in the normal host. Over the past year we have been able to demonstrate the kinetics of P. carinii infection in healthy mice. We have begun to conduct gene chip studies to try to identify immune mechanisms that are important in controlling infection in these animals. It is hoped that these studies will provide insights into the role of cytokines in P. carinii pneumonia, and may provide mechanisms for increasing clearance of P. carinii or decreasing the inflammation that may be causing hypoxia.